The Grubbs Reaction in Organic Synthesis

Alkene metathesis (e.g. 1 + 2 -> 3) has been known at
least since the 1950's. Until Robert Grubbs of Caltech developed stable and
versatile Ru catalysts for this transformation, however, this reaction was
little used.

Professor Grubbs recently published (J. Am. Chem. Soc.2003,
125, 10103.
/ J. Am. Chem. Soc.2003, 125, 11360.
)
two detailed articles on activation and selectivity in this reaction.
The first article addresses variations on catalyst design. The second paper
defines several types of alkenes, and lays out rules that allow one to predict
which pairs of alkenes will dimerize efficiently. While it is not possible to
summarize all of their results in this limited space, some highlights include:

It is also not possible to even partially review all the many applications in
synthesis that have already been demonstrated for the Grubbs reaction. I have
chosen to focus on three papers. For those desiring to deploy the Grubbs
catalyst only from time to time, storage and handling become serious issues. We
have found (J. Org. Chem.2003, 68, 6047.
)
that the commercial catalyst dissolved in paraffin wax can be stored
exposed to the laboratory atmosphere for many months and still retain full
activity. The example above of 1 + 2 -> 3 is taken from
that paper.

Steve Martin of UT Austin has reported (J. Org. Chem.2003,
68, 8867.
)
a detailed study of the synthesis of bridged azabicyclic structures via
ring-closing alkene metathesis. Some examples of his work include the conversion
of
12to 13, efficiently forming six, seven and eight membered
rings. He also demonstrated five-membered ring formation with the conversion of
14 to 15, which has the cocaine skeleton.

A real concern when attempting the Grubbs reaction with a complex substrate
is the stability of other alkenes. J. Alberto Marco of the University of
Valencia, Spain has shown (J. Org. Chem.,
2003, 68, 5672.
)
that
16 is converted to 17 without isomerization of the Z
alkene. Less congested alkenes might not be so resistant.